First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5- fluorouracil (DCF) plus panitumumab (P) in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction (GEJ): A phase II multicenter trial.

Abstract

146 Background: Gastric cancer is a highly aggressive disease. No established standard first-line regimens are currently available. Aim of this study is to evaluate efficacy of dose-dense chemotherapy with DCF combined with P in patients (pts) with locally advanced or metastatic cancer of the stomach or GEJ. Methods: HER2 negative, ECOG PS 0-1, not previously treated pts, received up to 4 cycles of therapy with Panitumumab 6 mg/kg d 1, Docetaxel 60 mg/m2 d 1, Cisplatin 50 mg/m2 d 1, L-Folinic acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2, and then 600 mg/m2 as a 22 h c.i. on d 1 and 2, every 2 weeks, plus Pegfilgrastim 6 mg on d 3. Pts aged ≥ 65 years were treated with the same chemotherapy schedule with a dose reduction by 30%. Pts with disease control after 4 cycles, received P until progression. Results: From 05/2010 to 01/2014, 52 consecutive pts were enrolled (75% M, 25% F; median age: 64.5 y, range: 42-75; metastatic 90%, locally advanced inoperable 10%; 96% adenocarcinoma; 13 pts with GEJ cancer). Primary end point was overall response rate (ORR). At 31 Aug 2014 cut-off date, 1 pt is still on treatment, 2 lost at f-up, 11 alive and 39 dead. 50 pts evaluable for response and all for toxicity. A median of 4 cycles (range 0-6) was administered. 3 CR, 29 PR, 10 SD and 8 PD were observed, for an ORR (by ITT) of 62% (95% CI, 48%-75) and a DCR of 81%. 26 pts entered the maintenance phase with only P and received a median 7.3 cycles (range 1-46). Median TTP was 4.8 months (95% CI, 4.1-6.9) and median OS was 9.4 months (95% CI, 7.4- 11.6). Most frequent grade 3-4 toxicities were: leucopenia (29%), neutropenia (19%), febrile neutropenia (13%), anemia (10%), asthenia (27%), mucosytis (13%), anorexia (17%), nausea/vomiting (12%), diarrhea (15%), ipokalemia (12%), and skin rash (25%). Two toxic deaths were registered (pulmonary aspergyllosis due to febrile neutropenia and gastric hemorrhage). Conclusions: Dose-dense chemotherapy combined with P is a very active regimen in gastric cancer. Due to a not negligible toxicity profile, it may represent a treatment option in neoadjuvant setting. Clinical trial information: 2009-016962-10.